The ABCD-USA Consortium proposes a study designed to permit the scientific community to answer important questions about the effects of substance use (SU) patterns on behavioral and brain development of adolescents. We have assembled a team of investigators with unparalleled research experience with children and adolescents, and specific expertise in adolescent SU, child and adolescent development, developmental psychopathology, longitudinal multi-site imaging, developmental neuroimaging, developmental cognitive neuroscience, genetics and imaging genetics, bioassays, epidemiology, survey research, bioinformatics, and mobile assessment technologies. We propose a comprehensive, nationwide study to be conducted at 21 sites organized into 11 hubs (over 89 million Americans, 29% of the US population, live within 50 miles of our geographically spread sites), that, uniquely, can provide a nationally representative sample and a large twin sample that together can help distinguish environmental, sociocultural, and genetic factors relevant to SU. We ensure cohesion and standardization by employing a recruitment strategy designed by a professional survey company (experience with Monitoring the Future); standardized environmental, neurocognitive and mental health assessments, MRI assessments with all scanners using harmonized Human Connectome Project procedures, and computerized data collection with real-time quality control. Developmentally tailored assessments will have stable sensitivity and construct validity across the childhood and adolescent developmental period. They minimize participant burden, yet capture even subtle changes over time in substance use, mental health, neurocognition, development, and environment, and we employ novel state-of-the-art bioassays and passive data collection from mobile devices. A detailed retention plan builds on the experience and success of our investigators. This application describes the ABCD-USA Data Analysis and Informatics Center (DAIC), which will: establish a harmonized MRI acquisition protocol, compatible with all major scanner platforms, taking advantage of recent technological advances in structural and functional MRI; establish rigorous quality control and quantitative calibration procedures to ensure accuracy and comparability of derived imaging measures across scanners and across time; implement advanced computational analysis workflows for all imaging data; implement reliable data entry, quality control, and monitoring tools for the substance use questionnaire, neurocognitive assessments, bioassay-derived measures, and mobile technologies assessment data; implement the state- of-the-art statistical analysis tools and procedures needed to integrate information across measures and modalities; and implement infrastructure and procedures for public sharing of raw- and derived data and associated tools and computational workflows, and enable interactive data exploration and analytics through a web-based Portal.